Velta L. Sparnins

Effects of allyl methyl trisulfide on glutathione S-transferase activity and BP-induced neoplasia in the mouse.

Allyl methyl trisulfide (AMT), a constituent of garlic oil, was studied for its effects on glutathione S-transferase (GST) activity and on benzo[a]pyrene (BP)-induced neoplasia of the forestomach and lungs of female A/J mice. AMT induced increased GST activity in the forestomach, small bowel mucosa, liver, and lung. The forestomach and small bowel mucosa responded to a single low dose of AMT (3.0 mumol) given by oral intubation, whereas liver and lung were less reactive. A dose schedule of two administrations of 15 mumol AMT given 48 hours apart gave close-to-maximum induction in all four tissues and was chosen for investigation of its inhibitory effects. With this dose schedule, AMT produced an inhibition of BP-induced neoplasia of the forestomach as shown by a greater than 70% reduction in the number of tumors found at the completion of the experiment. Inhibition of pulmonary neoplasia did not occur. AMT is a member of a new class of naturally occurring chemicals that have the capacity to inhibit chemical carcinogenesis.

Effects of cyclic 12-, 8-, and 6-carbon compounds on glutathione S-transferase activity

The effects of feeding ICR/Ha mice cyclic 12-, 8-, and 6-carbon compounds on glutathione S-transferase (GST) activity in the liver, intestinal mucosa, and the forestomach were determined. The compounds used for this study were 1,5,9-trans,trans,cis- cyclododecatriene , 1,2-trans-5,6-trans-9,10-cis- cyclododecatriene -1,2-oxide, cyclododecanol , cyclododecene oxide, cyclododecane , 1,5- cyclooctadiene , cyclooctene oxide, cyclohexene, and cyclohexene oxide. The unsaturated cyclic 12-carbon compounds elicited the greatest increase in GST activity. Thus, feeding 1,5,9-trans,trans,cis- cyclododecatriene increased this activity almost 4-fold in the livers and the intestinal mucosa of experimental animals. Cyclic 8-carbon compounds were less effective and feeding the cyclic 6-carbon compounds did not result in any significant increase in GST activity. None of the compounds elicited increased GST activity in the fore-stomach. Previous studies have shown that compounds inducing increased GST activity can protect against chemical carcinogens. It remains to be determined whether the compounds identified in the present investigation as inducers of this enzyme system will have such protective capacities.